Ameliorated effects of nattokinase on high‐fat diet and carrageenan‐induced tail‐thrombosis mice

Abstract BACKGROUND Thrombosis is the main cause of death as a result of cardiovascular diseases. However, the amelioration of thrombus by reshaping intestinal flora is rarely reported at present. In the present study, the activity of nattokinase (NK) from Bacillus natto fmb 401 reached 484.0 FU mL −1 at the end point of fermentation. NK was used to treat high‐fat diet (HFD)/carrageenan‐induced tail‐thrombosis mice. RESULTS NK supplementation lowered tail‐thrombus by 42.30%, increased fibrin degradation products (FDP) by 66.67% compared to those in the model group, reduced inflammation and blood fat, and increased antioxidant activity in mice with thrombosis induced by HFD and carrageenan. According to further research, NK administration reduced the ratio of Firmicutes to Bacteroidetes (F/B), and Firmicutes abundance and harmful bacteria Shigella , and also increased Bacteroidetes phylum abundance and Lactobacillus , Bacteroides and Parabacteroides genus abundance. In addition, significantly up‐regulated the mRNA expression of AMPK , FFAR2 , FFAR3 and ATGL and down‐regulated Acc mRNA expression were also observed, as a result of NK. CONCLUSlON All of these findings revealed that NK not only ameliorated HFD/carrageenan‐induced gut dysbiosis but also decreased blood lipids in tail‐thrombosis mice. The gut microbiota appeared to be important in regulating lipid metabolism, fat accumulation, inflammation and antioxidation. NK improve HFD/carrageenan‐induced tail‐thrombosis mice probably through regulating gut micribiota ( Bacteroides , Shigella , etc.), further improving liver and intestinal function, decreasing blood lipids and inflammatory cytokines, and increasing FDP levels to inhibit thrombus formation. Furthermore, NK combined with panax notoginseng (NK + S) demonstrated a better effect in improving tail‐thrombosis mice than that of NK alone. The present study provides a theoretical basis and new ideas for the application of NK in functional food. © 2025 Society of Chemical Industry.